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Issue 29, 2017
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A pH sensitive polymeric micelle for co-delivery of doxorubicin and α-TOS for colon cancer therapy

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Abstract

Combination therapy through simultaneous delivery of two or more therapeutic agents using nanocarriers has emerged as an advanced tactic for cancer treatment. To ensure that two therapeutic agents can be co-delivered and rapidly release their cargo in tumor cells, a biocompatible pH-sensitive copolymer, methoxy poly(ethylene glycol)-b-poly(hydroxypropyl methacrylamide-g-α-tocopheryl succinate-g-histidine) (abbreviated as PTH), was designed and synthesized. The PTH copolymers spontaneously self-assembled into micellar-type nanoparticles in aqueous solutions and are used for co-delivery of therapeutic agents, doxorubicin (Dox) and α-TOS. During micellization, π–π stacking occurred between Dox/α-TOS and imidazole rings of PTH copolymers inducing a regular and tight arrangement of copolymers and drugs to form rod-like micelles, thus efficiently increasing the drug loading and encapsulation efficiency. The micelles enabled the rapid release of both Dox and α-TOS when the pH decreased from 7.4 to 4.5. The protein adsorption assay revealed that low amounts of IgG and BSA were adsorbed on the micelles. In vivo biodistribution demonstrated that the micelles could largely accumulate in the tumor tissues. Furthermore, drug-loaded micelles treated with HCT116 cancer cells exhibited higher cytotoxicity than normal cells, which confirmed that α-TOS exhibited a synergy effect with Dox towards cancer cells, while no recognizable side effects were observed during the treatment from organ function tests.

Graphical abstract: A pH sensitive polymeric micelle for co-delivery of doxorubicin and α-TOS for colon cancer therapy

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Publication details

The article was received on 14 Apr 2017, accepted on 16 Jun 2017 and first published on 23 Jun 2017


Article type: Paper
DOI: 10.1039/C7TB01031A
Citation: J. Mater. Chem. B, 2017,5, 5870-5880
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    A pH sensitive polymeric micelle for co-delivery of doxorubicin and α-TOS for colon cancer therapy

    T. A. Debele, K. Lee, N. Hsu, Y. Chiang, L. Yu, Y. Shen and C. Lo, J. Mater. Chem. B, 2017, 5, 5870
    DOI: 10.1039/C7TB01031A

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